This invention relates to monoclonal antibodies.
Recent developments in hybridoma technology have demonstrated that human T cells can be divided into more than one functionally distinct subpopulation. For example, Reinherz et al., Cell, 19:821 (1980) and Reinherz et al., Immunology Today, 4:69 (1981) describe studies which indicate that certain T cell subsets have inducer functions, whereas other subsets have suppressor functions. Other studies have demonstrated that communicative interactions occur between and within the major T cell subsets in the generation of specific effector functions; Evans et al., J. Immunol., 120:1243 (1978); Morimoto et al., J. Immunol., 128:1645 (1982); Thomas et al., J. Immunol. 125:2402 (1980); Gatenby et al., J. Exp. Med., 156:55 (1982); and Yachi et al., J. Immunol., 129:103 (1982). Because regulatory mechanisms are essential to the maintenance of immune homeostasis, an understanding of the interactions between the subsets is of considerable importance.
It has been shown that within the major T cell sets T4 and T8 there exists both functional and phenotypic heterogeneity; Thomas et al., J. Immunol., 125: 2402 (1980); Morimoto et al., J. Immunol., 128: 1645 (1982); Gatenby et al., J. Exp. Med., 156: 55 (1982); and Reinherz et al., J. Immunol., 126: 67 (1981). Interaction between subpopulations of T4 and T8 cells, for example, is required to induce suppression of IgG production in antigen, pokeweed mitogen, or autologous leukocyte reaction-driven systems. Similarly, differentiation of T8 cytotoxic effectors from precytotoxic T8 lymphocytes in mixed leukocyte reactions has been shown to require the presence of T4 cells.
A number of monoclonal and autoantibodies have been developed which have provided an initial phenotypic definition of the heterogeneity within the major populations of these cells. Morimoto et al., J. Clin. Invest., 67: 753 (1981) describes using naturally occurring anti-T cell antibodies found in some patients with active juvenile rheumatoid arthritis (JRA) to subdivide T4 cells into helper population (T4JRA-) and an inducer of suppressor subpopulation (T4JRA+) for pokeweed mitogen and antigen driven immunoglobulin production. Similarly, Reinherz et al., J. Immunol., 128: 463 (1982) describes using antibody to Ia to divide T4 cells into T4Ia+ and T4Ia-subsets; both subsets were required to induce optimal Ig secretion by B cells.